This invention relates to a polysulfone type hollow fiber membrane for purifying blood and a process for producing the same. More particularly, it relates to a polysulfone type blood-purifying membrane which is improved in blood compatibility and separation properties and a process for producing the same.
In recent years, ultrapurificaiton methods, reverse osmosis methods, gas separation methods and the like which are separation techniques using a selectively permeable separation membrane have been put into practice in various fields, and separation membranes made from a material suitable to each of said various uses have been placed on the market. As a material for the selective, permeable separation membrane, there are used polymers of cellulose type, cellulose acetate type, polyamide type, polyacrylonitrile type, polyvinyl alcohol type, polymethyl methacrylate type, polysulfone type, polyolefin type and the like. Among them, polysulfone type polymers are excellent in physicochemical properties, such as thermal resistance, acid resistance, alkali resistance, oxidation resistance and the like, and therefore, attention has been paid thereto as recent medical and industrial separation membrane materials.
However, the polysulfone type polymers are hydrophobic materials, so that selectively permeable separation membranes made therefrom are inferior in water-wettability to selective, permeable separation membranes made from hydrophilic polymers. Therefore, such disadvantages have been pointed out that when the polysulfone type polymers are applied to medical uses, adsorption of plasma protein is easy to be caused, it is difficult for bubbles to go away, and hence, the bubbles left in the membranes would migrate into blood, activate platelets and cause coagulation of blood.
Therefore, an examination has been made for imparting hydrophilicity to a selective, permeable separation membrane made from a polysulfone type polymer to enhance its water-wettability. As one of the methods, there has been proposed a selectively permeable separation membrane prepared by incorporating a hydrophilic polymer into a polysulfone type polymer and a process for producing the same. However, it has such problems that when the amount of the hydrophilic polymer contained is small, the water-wettability becomes inferior thereby causing coagulation of blood, while when the amount of the hydrophilic polymer contained is large, the amount of the hydrophilic polymer eluted from the produced membrane becomes large.
JP-A-61-238,306 and JP-A-63-97,666 disclose a method for producing a polysulfone type separation membrane using, as a membrane-production polymer solution, a system formed by adding a polysulfone type polymer, a hydrophilic polymer and an additive which is a non-solvent or swelling agent for the polysulfone type polymer. However, they are silent on a method of decreasing the amount of the hydrophilic polymer eluted. In addition, JP-A-63-97,205, JP-A-63-97,634 and JP-A-4-300,636 (corresponding to European Patent Publication No. 0 509 663) disclose a method in which the polysulfone type separation membrane prepared by the above method is subjected to radiation treatment and/or thermal treatment to insolubilize the hydrophilic polymer, thereby decreasing the amount of the hydrophilic polymer eluted. However, since the hydrophilic polymer is insolubilized by this cross-linking, the blood compatibility becomes deteriorated.
JP-A-6-165,926 discloses a method for producing a hollow fiber membrane by subjecting a polysulfone type hollow fiber membrane, comprising a polyglycol and a vinylpyrrolidone type polymer, to water-washing and hot-water-washing treatments and then to treatment with a solution having a poor solvent action on the above polysulfone type polymer. However, this method is a step for adjusting the amount of the PVP existing on the internal surface side of the hollow fiber membrane so as to become 1.1 times the existing ratio and is not suitable for the purpose of extracting the excess PVP.
With respect to the draft ratio in spinning, in JP-B-5-54,373 (corresponding to European Patent Publication No. 0 168 783), a method is disclosed for producing a blood-treating, hollow fiber membrane which has been prepared by spinning a low-viscosity polymer solution consisting of a hydrophobic polymer, a hydrophilic polymer and a common solvent for them, and which contains the hydrophilic polymer in a proportion of 1 to 10% by weight and has a water-absorbing capacity of 3 to 10%, and in this publication, it is stated to be preferable that the velocity of extrusion of the spinning composition from the spinneret and the speed of taking off the resulting fibers are the same as each other, namely the draft ratio is 1. However, when the draft ratio is actually 1, it is difficult to increase the spinning velocity. When the amount of the polymer solution extruded is increased for increasing the spinning velocity, there are caused such problems that the pressure loss at the spinneret becomes large; the linear velocity of extrusion of the spinning polymer solution is increased; extrusion unevenness of the spinning polymer solution is easily caused; spinning becomes instable; membrane structures are disordered; and the like. In addition, in JP-A-6-165,926, it is proposed that the draft ratio is usually in the range of 2 to 5 because when the draft ratio is extremely increased or conversely decreased, the structure becomes instable; however, when the draft ratio exceeds 2, problems are encountered such as forming a structure in which the internal surface of the hollow fiber membrane has been torn, thereby causing albumin, a useful protein, to leak out easily.
Recently, low-molecular weight proteins such as xcex2-2-microglobulin and the like have been mentioned as causes of dialysis complication, and a dialysis membrane having high performance, so that it can remove them from the blood with good efficiency is desired. In the above-mentioned prior art, no sufficient examination has been made on fractionating properties and the examination has not been necessarily satisfactory. That is to say, this is because when the permeability of a membrane is enhanced for the purpose of improving the removal of the low-molecular weight proteins, the leak of useful proteins such as albumin and the like becomes an issue.
This invention aims at solving the issues of the prior art; improving blood compatibility; providing a polysulfone type blood-purifying membrane whose separation characteristics have been improved; and providing a process for producing the same.
The present inventors have diligently made an examination for achieving the above-mentioned purposes and have consequently found that a clean, hollow fiber membrane which is low in the amount of polyvinyl pyrrolidone (referred to hereinafter as PVP) eluted from the internal surface and excellent in blood compatibility, can be provided by water-insolubilizing a portion of the PVP of a PVP-containing polysulfone type hollow fiber membrane for purifying blood and adjusting the PVP concentration on the internal surface of the hollow fiber membrane to an appropriate value. Moreover, they have found that a clean, hollow fiber membrane which is lower in the amount of PVP eluted from the internal surface can be provided by extracting the PVP with an adequate solvent, thereby washing the hollow fiber membrane. In addition, they have found that by subjecting a polymer solution having an adequate viscosity to spinning at an appropriate draft ratio, there can be provided a polysulfone type hollow fiber membrane for purifying blood which membrane has sharp fractionating properties and in which membrane the thickness of selective separation layer having an effect of substantially screening the eluting molecules in the membrane, can be appropriately controlled; simultaneously the internal surface of the hollow fiber membrane has no torn structure; and the removal of unnecessary materials and recovery of useful materials can be conducted with good efficiency because the internal surface of the hollow fiber membrane has no torn structure.
That is to say, this invention is a polysulfone type hollow fiber membrane for purifying blood in which membrane a selective separation layer exists on the internal surface side of the hollow fiber membrane and which membrane contains polyvinyl pyrrolidone, wherein the polyvinyl pyrrolidone is contained in a proportion of 1 to 10% by weight, 5% to 50% by weight of the polyvinyl pyrrolidone is soluble in water, and the concentration of the polyvinyl pyrrolidone on the internal surface is in the range of 30% to 45%.
This invention is also a process for producing a polysulfone type hollow fiber membrane for purifying blood, which comprises subjecting a polymer solution comprising 15 to 20% by weight of a polysulfone type polymer in which solution the weight ratio of polyvinyl pyrrolidone to the polysulfone type polymer is from 0.25 to 0.5, to extrusion at a viscosity of 1,500 to 6,000 mPaxc2x7s, and to spinning at a draft ratio of 1.1 to 1.9 and at a linear extrusion velocity of not more than 90 m/min.
Moreover, this invention is a process for producing a polysulfone type hollow fiber membrane for purifying blood, which comprises spinning a hollow fiber membranes using a polymer solution which comprises 15 to 20% by weight of a polysulfone polymer in which solution the weight ratio of polyvinyl pyrrolidone to the polysulfone type polymer is from 0.25 to 0.5, and thereafter insolubilizing a portion of the polyvinyl pyrrolidone in the hollow fiber membrane by a physicochemical method.